Opioid peptides are an important class of bioregulators, involved in pain recognition, and gastric, respiratory, and behavioral processes. To supply opioid peptides for research use and eventually pharmaceutical use, new methodologies for the synthesis of opioid peptides must be developed that avoid the problems of current techniques. This program is aimed at the development of a novel peptide segment- coupling process that overcomes the disadvantages of chemical and conventional enzymatic segment-coupling methods. the approach is based on the use of an enzyme process that is used to couple peptide segments together. When this process is used in conjunction with a novel set of protecting groups, the drawbacks commonly associated with chemical and conventional enzymatic segment-coupling methods are avoided (e.g., racemization of activated carboxyl components, the necessity of side-chain protection, and the use of polar solvents that are difficult to handle). In Phase II, we propose to expand the technology to apply it to a variety of opioid peptides of increasing lengths and to develop the information necessary to commercialize the process in Phase III. Specifically, we will seek to demonstrate that the process is generally applicable to different peptides and that process is economically feasible.